This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Spiller, O. B.
Right arrow Articles by Blackbourn, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Spiller, O. B.
Right arrow Articles by Blackbourn, D. J.

 Previous Article  |  Next Article 

Journal of Virology, January 2003, p. 592-599, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.592-599.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Complement Regulation by Kaposi's Sarcoma-Associated Herpesvirus ORF4 Protein

O. Brad Spiller,1 Mairi Robinson,2 Elizabeth O'Donnell,2 Steven Milligan,2 B. Paul Morgan,1 Andrew J. Davison,3 and David J. Blackbourn2*

Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff CF14 4XX,1 Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow,2 MRC Virology Unit, Glasgow G11 5JR, United Kingdom3

Received 11 July 2002/ Accepted 30 September 2002

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with three types of human tumor: Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. The virus encodes a number of proteins that participate in disrupting the immune response, one of which was predicted by sequence analysis to be encoded by open reading frame 4 (ORF4). The predicted ORF4 protein shares homology with cellular proteins referred to as regulators of complement activation. In the present study, the transcription profile of the ORF4 gene was characterized, revealing that it encodes at least three transcripts, by alternative splicing mechanisms, and three protein isoforms. Functional studies revealed that each ORF4 protein isoform inhibits complement and retains a C-terminal transmembrane domain. Consistent with the complement-regulating activity, we propose to name the proteins encoded by the ORF4 gene collectively as KSHV complement control protein (KCP). KSHV ORF4 is the most complex alternatively spliced gene encoding a viral complement regulator described to date. KCP inhibits the complement component of the innate immune response, thereby possibly contributing to the in vivo persistence and pathogenesis of this virus.

* Corresponding author. Mailing address: Institute of Virology, University of Glasgow, Church St., Glasgow G11 5JR, United Kingdom. Phone: 44 (0)141 330 3685. Fax: 44 (0)141 337 2236. E-mail: d.blackbourn{at}vir.gla.ac.uk.

Journal of Virology, January 2003, p. 592-599, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.592-599.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pyaram, K., Kieslich, C. A., Yadav, V. N., Morikis, D., Sahu, A. (2010). Influence of Electrostatics on the Complement Regulatory Functions of Kaposica, the Complement Inhibitor of Kaposi's Sarcoma-Associated Herpesvirus. J. Immunol. 184: 1956-1967 [Abstract] [Full Text]  
  • Spiller, O. B., Mark, L., Blue, C. E., Proctor, D. G., Aitken, J. A., Blom, A. M., Blackbourn, D. J. (2006). Dissecting the Regions of Virion-Associated Kaposi's Sarcoma-Associated Herpesvirus Complement Control Protein Required for Complement Regulation and Cell Binding. J. Virol. 80: 4068-4078 [Abstract] [Full Text]  
  • Mullick, J., Singh, A. K., Panse, Y., Yadav, V., Bernet, J., Sahu, A. (2005). Identification of Functional Domains in Kaposica, the Complement Control Protein Homolog of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8). J. Virol. 79: 5850-5856 [Abstract] [Full Text]  
  • Mark, L., Lee, W. H., Spiller, O. B., Proctor, D., Blackbourn, D. J., Villoutreix, B. O., Blom, A. M. (2004). The Kaposi's Sarcoma-associated Herpesvirus Complement Control Protein Mimics Human Molecular Mechanisms for Inhibition of the Complement System. J. Biol. Chem. 279: 45093-45101 [Abstract] [Full Text]  
  • Tomescu, C., Law, W. K., Kedes, D. H. (2003). Surface Downregulation of Major Histocompatibility Complex Class I, PE-CAM, and ICAM-1 following De Novo Infection of Endothelial Cells with Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 77: 9669-9684 [Abstract] [Full Text]  
  • Spiller, O. B., Blackbourn, D. J., Mark, L., Proctor, D. G., Blom, A. M. (2003). Functional Activity of the Complement Regulator Encoded by Kaposi's Sarcoma-associated Herpesvirus. J. Biol. Chem. 278: 9283-9289 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»